PDGFRA (platelet-derived growth factor receptor, alpha polypeptide)

4q12

Composed of an extracellular domain, a transmembrane domain, a juxtamembrane domain, and an intracellular domain; receptor tyrosine kinase; forms homodimer, and heterodimer with PDGFRB ; dimerization induces kinase domain activation, leading to the activation of intracellular signalling pathways (Kawagishi et al, 1995).

Hybrid genes between various partners and PDFRGA occur in chronic myeloid leukaemia-like diseases with eosinophilia, mostly chronic eosinophilic leukemia (CEL), a clonal hypereosinophilic syndrome. PDGFRA partners known so far are: STRN (2p24) (Curtis et al, 2007), FIP1L1 (4q12) (Cools et al, 2003; Pardanani et al, 2004), CDK5RAP2 (9q33) (Walz et al, 2006), KIF5B (10p11) (Score et al, 2006), ETV6 (12p13) (Curtis et al, 2007), and BCR (22q11) (Baxter et al, 2002).
Mutations of platelet-derived growth factor receptor-alpha (PDGFRA) are observed in a subset of gastrointestinal stromal tumors (GISTs) (Heinrich et al, 2003).
Tumours with PDGFRA involvement are responsive to imatinib therapy (Cools et al, 2003; Debiec-Rychter et al, 2004).

KIF5B (kinesin family member 5B)

10p11.22

Composed of a N-terminal globular domain that hydrolyzes ATP and binds microtubule, a central alpha-helical coiled-coil domain (dimerization domain); and a C-terminal domain that interacts with other proteins, vesicles and membranous organelles. Kif5B is involved in microtubule-based polarized vesicular transport to the apical membrane in polarized axonal transport in neurons (Nakata and Hirokawa, 2003; Jacobson et al, 2007; Jaulin and Mostov, 2007). The role of the complex of syntaxin-1-syntabulin-KIF5B in axonal transport has been established (Cai et al, 2007). Kif5B and Kifc1 interact in motility and processing of early endocytic vesicles (Nath et al, 2007). KIF5B has been shown to be essential for axonal transport of mitochondria. KIF5B associates with the kinesin-binding domain (KBD) of RanBP2 to determines mitochondria localization (Cho et al, 2007). JNK forms a complex with KIF5B and ß-tubulin-III in neurites, and TNF disturbs axonal transport of mitochondria via JNK (Stagi et al, 2006).